Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs
Abstract Background Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to l...
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| Language: | English |
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BMC
2024-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03628-6 |
| _version_ | 1797350095679651840 |
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| author | Koichiro Iohara Michiyo Tominaga Hideto Watanabe Misako Nakashima |
| author_facet | Koichiro Iohara Michiyo Tominaga Hideto Watanabe Misako Nakashima |
| author_sort | Koichiro Iohara |
| collection | DOAJ |
| description | Abstract Background Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs. Methods Periapical lesions were induced in 32 root canals of 4 dogs in two different models in severities, model A and model B. Model A (moderate infection): the canal exposed to the oral cavity for 2 weeks and then closed for 2 weeks. Model B (severe infection): the canal exposed to the oral cavity for 2 months and then closed for 5 months. All root canals were irrigated with 6% sodium hypochlorite, and 3% EDTA and further with 0.015% levofloxacin-containing nanobubbles, which was also used as an intracanal medicament. The aseptic conditions were examined by bacterial anaerobic culture and/or PCR analyses. The root canal treatment was repeated several times, and allogeneic dental pulp stem cells were transplanted into the root canals. The radiographic evaluation of periapical lesions was performed by cone-beam computed tomography before the first treatment, just after cell transplantation, and after 2 months and 6 months in both model A, model B, respectively. The animals were then sacrificed and the jaw blocks were harvested for histological and histobacteriological evaluations of pulp regeneration and periapical tissue healing. Furthermore, the DiI-labelled DPSCs were transplanted into the root canals after complete disinfection (n = 4) or without root canal treatment (n = 4) in the apical periodontitis model (model A) in one dog, and cell localization was compared 72 h after transplantation. Results In 8 out of 12 canals from model A, and 10 out of 15 canals from model B, pulp regeneration with good vascularization, innervation, and a significant reduction in the radiolucent area of the periapical lesions were observed. However, in the other 4 canals and 5 canals from model A and model B, respectively, no pulp tissue was regenerated, and inflammation in the periapical tissue, and external resorption or healed external resorption were detected. The presence of residual bacteria in the periapical tissues and severe inflammation were significantly associated with inhibition of regenerated pulp tissue in these 9 unsuccessful canals (P < 0.05, each) (OR = 0.075, each) analyzed by multiple logistic regression analysis. For cellular kinetics, transplanted cells remained in the disinfected root canals, while they were not detected in the infected root canals, suggesting their migration through the apical foramen under the influence of inflammation. Conclusions A true pulp-dentin complex was regenerated in the root canal by the pulp regenerative therapy in mature teeth with apical lesions. The successful pulp regeneration was negatively associated both with residual bacteria and inflammation in the periapical tissue. |
| first_indexed | 2024-03-08T12:40:50Z |
| format | Article |
| id | doaj.art-e388da54bb004f5a93dca711f3e9687d |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-08T12:40:50Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e388da54bb004f5a93dca711f3e9687d2024-01-21T12:12:54ZengBMCStem Cell Research & Therapy1757-65122024-01-0115111410.1186/s13287-023-03628-6Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogsKoichiro Iohara0Michiyo Tominaga1Hideto Watanabe2Misako Nakashima3Section of Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research CenterSection of Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research CenterInstitute for Molecular Science of Medicine, Aichi Medical UniversitySection of Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research CenterAbstract Background Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs. Methods Periapical lesions were induced in 32 root canals of 4 dogs in two different models in severities, model A and model B. Model A (moderate infection): the canal exposed to the oral cavity for 2 weeks and then closed for 2 weeks. Model B (severe infection): the canal exposed to the oral cavity for 2 months and then closed for 5 months. All root canals were irrigated with 6% sodium hypochlorite, and 3% EDTA and further with 0.015% levofloxacin-containing nanobubbles, which was also used as an intracanal medicament. The aseptic conditions were examined by bacterial anaerobic culture and/or PCR analyses. The root canal treatment was repeated several times, and allogeneic dental pulp stem cells were transplanted into the root canals. The radiographic evaluation of periapical lesions was performed by cone-beam computed tomography before the first treatment, just after cell transplantation, and after 2 months and 6 months in both model A, model B, respectively. The animals were then sacrificed and the jaw blocks were harvested for histological and histobacteriological evaluations of pulp regeneration and periapical tissue healing. Furthermore, the DiI-labelled DPSCs were transplanted into the root canals after complete disinfection (n = 4) or without root canal treatment (n = 4) in the apical periodontitis model (model A) in one dog, and cell localization was compared 72 h after transplantation. Results In 8 out of 12 canals from model A, and 10 out of 15 canals from model B, pulp regeneration with good vascularization, innervation, and a significant reduction in the radiolucent area of the periapical lesions were observed. However, in the other 4 canals and 5 canals from model A and model B, respectively, no pulp tissue was regenerated, and inflammation in the periapical tissue, and external resorption or healed external resorption were detected. The presence of residual bacteria in the periapical tissues and severe inflammation were significantly associated with inhibition of regenerated pulp tissue in these 9 unsuccessful canals (P < 0.05, each) (OR = 0.075, each) analyzed by multiple logistic regression analysis. For cellular kinetics, transplanted cells remained in the disinfected root canals, while they were not detected in the infected root canals, suggesting their migration through the apical foramen under the influence of inflammation. Conclusions A true pulp-dentin complex was regenerated in the root canal by the pulp regenerative therapy in mature teeth with apical lesions. The successful pulp regeneration was negatively associated both with residual bacteria and inflammation in the periapical tissue.https://doi.org/10.1186/s13287-023-03628-6Pulp regeneration apicalPeriodontitisDental pulp stem cellsAllogeneic cell transplantationPeriradicular disinfection |
| spellingShingle | Koichiro Iohara Michiyo Tominaga Hideto Watanabe Misako Nakashima Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs Stem Cell Research & Therapy Pulp regeneration apical Periodontitis Dental pulp stem cells Allogeneic cell transplantation Periradicular disinfection |
| title | Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| title_full | Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| title_fullStr | Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| title_full_unstemmed | Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| title_short | Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| title_sort | periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs |
| topic | Pulp regeneration apical Periodontitis Dental pulp stem cells Allogeneic cell transplantation Periradicular disinfection |
| url | https://doi.org/10.1186/s13287-023-03628-6 |
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